Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

High Dose Flu Vaccine in Treating Children Who Have Undergone Donor Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02860039
Recruitment Status : Active, not recruiting
First Posted : August 9, 2016
Last Update Posted : April 16, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Natasha Halasa, MD, Vanderbilt-Ingram Cancer Center

Brief Summary:
This phase II randomized trial studies how well high dose flu vaccine works in treating children who have undergone done stem cell transplant. Higher dose flu vaccine may build a better immune response and may provide better protection against the flu than the standard vaccine.

Condition or disease Intervention/treatment Phase
Hematopoietic Cell Transplantation Recipient Malignant Neoplasm Influenza Biological: Trivalent Influenza Vaccine Biological: Quadrivalent Influenza Vaccine Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether high-dose trivalent inactivated influenza vaccine (HD-TIV) compared with standard dose quadrivalent inactivated influenza vaccine (QIV) will increase the probability of achieving a >= 4-fold rise in hemagglutination-inhibition (HAI) titers, >= 1:40 HAI titer, or higher geometric mean titer (GMT) to influenza A antigens in pediatric hematopoietic stem cell transplant (HSCT) recipients.

SECONDARY OBJECTIVES:

I. To determine whether HD-TIV compared with standard dose QIV will increase the probability of achieving a >= 4-fold rise in HAI titers, >= 1:40 HAI titer, or higher GMT titers to influenza B antigens in pediatric HSCT recipients.

II. To determine the frequency and severity of solicited local injection site adverse events (e.g. pain/ tenderness, redness, and swelling at injection site) with HD-TIV compared to standard QIV in pediatric HSCT recipients.

III. To determine the frequency and severity of solicited systemic adverse events (e.g. fevers, headache, fatigue/malaise, nausea, body ache/myalgia, general activity level, and vomiting) with HD-TIV compared to standard dose QIV in pediatric HSCT recipients.

IV. To define the relationship between HAI titers, in vivo T and B cell phenotype, and in vitro influenza-specific T and B cell response in pediatric HSCT recipients receiving either HD-TIV or standard dose QIV.

V. To correlate HAI responses to microneutralization responses.

VI. To compare the persistent HAI and microneutralization (MN) titers for all four antigen seven months after the last vaccine dose to assess for persistence of antibody titers.

VII. To compare influenza detection by PCR during influenza season in pediatric HSCT recipients receiving either HD-TIV or standard dose QIV.

VIII. To assess HAI and MN response in children vaccinated during year 1 and revaccinated during year 2 using the same antigen dose.

OUTLINE: Patients are randomized to 1 of 2 treatment groups.

GROUP I (Experimental): Patients receive HD-TIV intramuscularly (IM) on day 0 and day 28.

GROUP II (Standard): Patients receive standard dose QIV IM on day 0 and day 28.

After completion of study treatment, patients are followed up at 28-42 days, and at 7 months.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Comparison of High vs. Standard Dose Flu Vaccine in Pediatric Stem Cell Transplant Recipients
Actual Study Start Date : September 2016
Actual Primary Completion Date : March 2020
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Group 1 - High Dose HD-TIV
Patients receive HD-TIV intramuscularly (IM) on day 0 and day 28.
Biological: Trivalent Influenza Vaccine
High dose Trivalent Influenza Vaccine given intramuscular

Other: Laboratory Biomarker Analysis
Correlative studies

Active Comparator: Group 2 - Standard Dose QIV
Patients receive standard dose QIV IM on day 0 and day 28.
Biological: Quadrivalent Influenza Vaccine
Standard dose Quadrivalent Influenza Vaccine given intramuscular

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Immunogenicity as measured by the number of subjects who achieve a 4-fold (or greater) rise in post-vaccination HAI titers [ Time Frame: Baseline up to 7 months after the second vaccination ]

Secondary Outcome Measures :
  1. Incidence and severity of solicited local injection site adverse events [ Time Frame: Up to 7 days following each vaccination ]
  2. T and B cell phenotype assessed by mass cytometry [ Time Frame: Up to 7 months after second vaccination ]
  3. T and B cell response assessed by mass cytometry and in-vitro functionality assays [ Time Frame: Up to 7 months after second vaccination ]
  4. Percentage of individuals in each group who test positive for influenza [ Time Frame: During the influenza season, up to 6 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

FOR YEAR 2:

A. A target of at least 200 pediatric patients who received an allogeneic HSCT

  1. Inclusion criteria

    • Allogeneic HSCT recipients who are 3-35 months post-transplant;
    • 3-17 years of age, inclusive;
    • Available for duration of study;
    • If patients are on immunosuppressive therapy for treatment of GVHD, then only those on stable doses for at least 4 weeks (or on tapering doses) will be eligible;
    • Parent/legal guardian willing and capable of signing written informed consent;
    • Parent/legal guardian expected to be available for entire study;
    • Parent/legal guardian can be reached by telephone or email.
    • Subjects must have a platelet count of ≥30,000 to receive the immunizations. Patients requiring platelet transfusions are eligible to enroll and must have a platelet count ≥30,000 within 72 hours prior to their immunization, or platelet count ≥75,000 without transfusion documented within 30 days for subjects <12 months post-transplant and within 90 days for subjects 12-35 months post-transplant.
    • Recipients of CD34 selected grafts or other manipulated grafts (with any form of ex vivo T cell depletion) will be eligible to enroll if they have a CD3 count >100. (Please note: post-transplant cytoxan for haploidentical transplants is allowable).
  2. Exclusion criteria

    • History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein;
    • History of Guillain-Barre syndrome;
    • Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerisms is permitted);
    • History of receiving current year seasonal influenza vaccine influenza vaccine;
    • Pregnant female;
    • History of proven influenza disease after September 1, 2017
    • Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients;
    • History of known active infection with HIV, Hepatitis B or Hepatitis C;
    • History of known severe latex hypersensitivity;
    • Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days of enrollment, including day of enrollment
    • Receipt of IVIG <27 days prior to calendar day of vaccination Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a subject may be included in the study once the condition has resolved, provided that the subject is otherwise eligible: 1). Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of enrollment 2). Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks of study vaccination.

B. For the 31 subjects enrolled in year 1, inclusion and exclusion criteria include:

  1. Inclusion criteria

    • If patients are on immunosuppressive therapy for treatment of GVHD, then only those on stable doses for at least 4 weeks (or on tapering doses) will be eligible;
    • Subjects must have a platelet count of ≥30,000 to receive the immunizations. Patients requiring platelet transfusions are eligible to enroll and must have a platelet count ≥30,000 within 72 hours prior to their immunization, or platelet count ≥75,000 without transfusion documented within 30 days for subjects <12 months post-transplant and within 90 days for subjects 12-35 months post-transplant.
    • Recipients of CD34 selected grafts or other manipulated grafts (with any form of ex vivo T cell depletion) will be eligible to enroll if they have a CD3 count >100. (Please note: post-transplant cytoxan for haploidentical transplants is allowable).
  2. Exclusion criteria

    • Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerisms is permitted);
    • History of receiving current year seasonal influenza vaccine influenza vaccine;
    • Pregnant female;
    • History of proven influenza disease after September 1, 2017
    • History of known active infection with HIV, Hepatitis B or Hepatitis C;
    • Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days of enrollment, including day of enrollment
    • Receipt of IVIG <27 days prior to calendar day of vaccination

Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a subject may be included in the study once the condition has resolved, provided that the subject is otherwise eligible: 1). Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of enrollment 2). Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks of study vaccination.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02860039


Locations
Layout table for location information
United States, California
UCSF Children's Hospital
San Francisco, California, United States, 94158
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital Research Institute
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Natasha Halasa, MD, MPH Vanderbilt University
Layout table for additonal information
Responsible Party: Natasha Halasa, MD, Associate Professor of Pediatrics, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT02860039    
Other Study ID Numbers: VICC PED 1647
NCI-2016-01090 ( Registry Identifier: Clinical Trial Reporting Program )
First Posted: August 9, 2016    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs